Supplementary Material for: Growth Differentiation Factor 15 Is Superior to Troponin I in the Evaluation of Kidney Transplant Candidates

<b><i>Introduction:</i></b> Pretransplant cardiac troponin I (cTNI) has demonstrated its predicting value in survival after kidney transplant. Growth differentiation factor 15 (GDF-15) is a biomarker currently studied as a predictor of mortality and cardiovascular events (CVE) in different scenarios. The aim of this study was to compare the utility of these two biomarkers in the prediction of events after kidney transplant. <b><i>Methods:</i></b> We included 359 kidney transplants performed in our center between 2005 and 2015. cTNI and GDF-15 were measured on stored serum samples obtained pretransplant. <b><i>Results:</i></b> Median GDF-15 was 5,346.4 pg/mL, and cTNI was 5.6 ng/L. After follow-up, 77 (21.5%) patients died, and the incidence of cerebrovascular accident (CVA), acute coronary syndrome (ACS), and major adverse CVEs (MACE) was 6.38%, 12.68%, and 20.56%, respectively. Patients were stratified in tertiles according to GDF-15 and cTNT levels. By multivariate cox regression analysis including both biomarkers and different clinical characteristics, we found a significant relation between GDF-15 and mortality, CVAs, and MACE (highest tertile hazard ratio [HR] 2.2 95% confidence interval [CI] [1.2–4.1], <i>p</i> = 0.01, HR 9.7 CI 95% [2.2–43.1], <i>p</i> = 0.003 and HR 2.7 CI 95% [1.4–5.1], <i>p</i> = 0.002). On the contrary, posttransplant ACS was related to cTNI (highest cTNI tertile HR 3.2 CI 95% [1.5–7.3], <i>p</i> = 0.003). <b><i>Discussion:</i></b> Our study indicates the potential utility of GDF-15 as a mortality and CVE predictor after kidney transplant and its superiority compared to cTNI. By contrast, probably due to its tissue specificity, cardiac troponin showed a stronger correlation with acute coronary events. Although more studies are needed to confirm our findings, these two molecules could be used in conjunction with other tools to predict adverse events after transplant and ideally find strategies to minimize them.

<b><i>引言：</i></b> 移植前心肌肌钙蛋白I（cardiac troponin I, cTNI）已被证实可用于预测肾移植术后的生存情况。生长分化因子15（growth differentiation factor 15, GDF-15）是目前在多种临床场景中被研究的生物标志物，用于预测死亡率与心血管事件（cardiovascular events, CVE）。本研究旨在对比这两种生物标志物在肾移植术后不良事件预测中的应用价值。
<b><i>方法：</i></b> 本研究纳入2005年至2015年间本中心完成的359例肾移植手术。对移植前留存的血清样本，检测受试者的cTNI与GDF-15水平。
<b><i>结果：</i></b> 受试者GDF-15的中位数为5346.4 pg/mL，cTNI的中位数为5.6 ng/L。经过随访后，共有77例（21.5%）患者死亡；脑血管意外（cerebrovascular accident, CVA）、急性冠状动脉综合征（acute coronary syndrome, ACS）以及主要不良心血管事件（major adverse CVEs, MACE）的发生率分别为6.38%、12.68%与20.56%。研究人员根据GDF-15与心肌肌钙蛋白T（cardiac troponin T, cTNT）水平将受试者分为三分位组。通过纳入两种生物标志物及多项临床特征的多变量Cox回归分析显示，GDF-15与死亡率、脑血管意外及主要不良心血管事件存在显著关联：最高三分位组的风险比（hazard ratio, HR）分别为2.2（95%置信区间（confidence interval, CI）：1.2–4.1），*p*=0.01；HR为9.7（95%CI：2.2–43.1），*p*=0.003；HR为2.7（95%CI：1.4–5.1），*p*=0.002。与之相反，移植后急性冠状动脉综合征与cTNI水平相关：最高cTNI三分位组的HR为3.2（95%CI：1.5–7.3），*p*=0.003。
<b><i>讨论：</i></b> 本研究结果表明，GDF-15作为肾移植术后死亡率与心血管事件的预测标志物具有潜在应用价值，且其预测效能优于cTNI。相较而言，由于心肌肌钙蛋白具有组织特异性，其与急性冠脉事件的相关性更强。尽管尚需更多研究以验证本研究结论，但这两种生物标志物可与其他辅助工具联合使用，用于预测移植术后不良事件，并有望为制定降低不良事件风险的策略提供依据。